2,3,7,8-TCDD exposure, endothelial dysfunction and impaired microvascular reactivity.

Vascular function was examined in subjects with long-term high level of serum 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) during their follow-up visits. Their earlier mean peak TCDD level at the time of exposure in 1965-1968 was estimated in the range of 3300-74 000 pg/g lipids. Ten former pesticide production workers heavily exposed to TCDD (age 57 +/- 2 years, TCDD about 170 pg/g lipids) were examined in 2001. Extended group of 15 TCDD-exposed men (age 59 +/- 3 years, TCDD about 130 pg/g lipids) underwent the same examination in 2004. Findings were compared with a control group of 14 healthy men (age 54 +/- 2 years). Skin microvascular reactivity (MVR) was measured by laser Doppler perfusion monitoring in the forearm during post-occlusive reactive hyperemia (PORH) and thermal hyperemia (TH). Several parameters of MVR in men exposed to TCDD were significantly impaired, compared with the control group and further progression of the impairment of MVR has been observed between years 2001 and 2004. Serum concentration of E-selectin and inhibitor of tissue plasminogen activator 1 (PAI-1) was significantly higher in exposed subjects (56.0 +/- 18.4 ng/mL versus 40.0 +/- 12.0 ng/mL, P = 0.022 and 90.9 +/- 33.3 ng/mL versus 45.0 +/- 18.0, P = 0.002, respectively). In addition, PORH in the forearm was significantly negatively associated with SOD activity (r = -0.77, P = 0.009) as well as the velocity of perfusion increase during TH (r = -0.68, P = 0.03) and TH% (r = -0.78, P = 0.008). Our data document the presence of endothelial dysfunction in TCDD-exposed men.

Occupational asthma and rhinitis in workers from a lasamide production line.

OBJECTIVES: A wide range of low-molecular-weight agents can cause occupational asthma. The chemical industry is an environment in which numerous hazardous substances are used. Lasamide (2,4-dichloro-5-sulfamoylbenzoic acid) is one of them (along with its precursors). METHODS: Five patients from a lasamide production line with suspected occupational asthma and rhinitis were examined. During the first visit, skin prick tests, total immunoglobulin E (IgE), a nonspecific bronchoprovocation test, and specific bronchoprovocation tests using occupational agents were performed to confirm the diagnosis of allergic diseases. During the follow-up visit (1-3 years after removal from exposure), all of the tests (except the specific bronchoprovocation test) were performed again. RESULTS: At the first hospitalization, the total IgE levels were increased in three patients. In addition, skin prick tests and the nonspecific bronchoprovocation test were positive for three patients. After the specific bronchoprovocation test, serious bronchoconstriction occurred in three patients; symptoms of rhinitis were present in all five patients. Several years after removal from exposure to the occupational agents, normalization (with respect to the parameters followed) was not yet complete for all of the patients. CONCLUSIONS: The process of lasamide production seems to be hazardous and is likely to cause allergic respiratory disease. The prognosis of allergic diseases caused by these products is not very favorable. Allergic symptoms (despite the removal from occupational allergen exposure) persisted even after several years.

Adverse health effects in humans exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

The environmental contaminant 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) belongs to the category of highly toxic, persistent organic pollutants that accumulate in animal fat and plant tissues. Today, background TCDD levels in human fat are showing a decreasing trend. The food chain is the main source of exposure in the human population. TCDD regulates the expression of a wide range of drug-metabolizing enzymes and has an impact on a large number of biological systems. The most pronounced effects have occurred in occupational settings following the uncontrolled formation of TCDD after industrial accidents, as well as in rare intentional intoxications. Although the acute effects of TCDD exposure are well described in the literature, the long-term consequences have been underevaluated. The most well-known symptoms of severe acute intoxication are chloracne, porphyria, transient hepatotoxicity, and peripheral and central neurotoxicity. Because of the long-term persistence of TCDD in the human body, atherosclerosis, hypertension, diabetes, vascular ocular changes, and signs of neural system damage, including neuropsychological impairment, can be present several decades after massive exposure. Such chronic effects are nonspecific, multifactorial, and may be causally linked to TCDD only in heavily intoxicated subjects. This opinion is supported by the dose-dependent effect of TCDD found in exposed workers and by experimental animal studies.